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Infarction, Middle Cerebral ArteryPhase 2/3ESSNCT00604630

Multicenter Efficacy Study of Recombinant Human Erythropoietin in Acute Ischemic Stroke

A Phase 2/3 study testing recombinant human erythropoietin alfa and 0.9% NaCl in people with Infarction, Middle Cerebral Artery and Middle Cerebral Artery Stroke, run by Max-Planck-Institute of Experimental Medicine at 9 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this randomized, double-blind, placebo-controlled multicenter study is to determine in a cohort of 506 patients with acute ischemic stroke in the middle cerebral artery territory, the effect of a three-day high-dose, intravenous erythropoietin treatment on functional outcome up to a follow-up of 90 days. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
recombinant human erythropoietin alfa and 0.9% NaCl
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
522 participants
Where
9 sitesGermany
Study dates
Jan 2003to Jun 2008
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ischemic stroke in the middle cerebral artery territory
  • Clearly defined time of onset
  • Confirmed by MRI (DWI, Flair)
  • NIH Stroke Scale ≥ 5
  • Age > 18 years
  • Treatment within 6h after onset of symptoms
  • Informed consent by patient, relatives or independent physician
  • Life expectancy > 90 days

Who cannot join

  • Coma or precoma (level of consciousness ≥ 2 in NIH Stroke Scale)
  • Previous stroke within the same territory
  • Intracranial or subarachnoidal hemorrhage
  • Traumatic brain injury or brain operation within the last 4 weeks
  • Neoplasia, septic embolism, infectious endocarditis
  • MRI contraindications
Show all 12Show fewer
  • Renal failure (i.e. dependent on dialysis)
  • Known malignant/life-threatening disease
  • Known myeloproliferative disorder, polycythemia
  • Known allergy or antibodies against erythropoietin
  • Participation in other intervention trials
  • Pregnancy

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites
  • Neurologische Klinik des Städtischen Klinikums Braunschweig

    Braunschweig, D-38126

  • Neurologische Klink, Klinikum Bremen-Mitte

    Bremen, D-28177

  • Neurologische Klinik, Allgemeines Krankenhaus Celle

    Celle, D-29223

  • Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus der TU Dresden

    Dresden, D-01307

  • Neurologische Klinik, Universität Erlangen-Nürnberg

    Erlangen, D-91054

  • Klinik für Neurologie, Universität Essen

    Essen, D-45147

  • Neurologische Universitätsklinik der Georg-August-Universität Goettingen

    Göttingen, D-37075

  • Neurologische Klinik, Medizinische Hochschule Hannover

    Hanover, D-30625

  • Klinik und Poliklinik für Neurologie der Universität Leipzig

    Leipzig, D-04103

Other trials in Germany

About this study

Official title: German Multicenter EPO Stroke Trial (Phase II/III)

The purpose of this randomized, double-blind, placebo-controlled multicenter study is to determine in a cohort of 506 patients with acute ischemic stroke in the middle cerebral artery territory, the effect of a three-day high-dose, intravenous erythropoietin treatment on functional outcome up to a follow-up of 90 days.

Being tested
recombinant human erythropoietin alfa, 0.9% NaCl
Keywords
stroke, EPO, erythropoietin, ischemia, hypoxia, antiapoptosis, neuroprotection, rtPA, thrombolysis, stroke, middle cerebral artery, Ischemic stroke in the middle cerebral artery territory
Medical subject headings
Infarction, Middle Cerebral Artery, Stroke, Ischemia, Hypoxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • recombinant human erythropoietin alfaDrug

    Also called ERYPO

    40,000 IU in 50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms

  • 0.9% NaClDrug

    50ml 0.9% NaCl iv on 3 consecutive days, starting within 6 hours after onset of symptoms

Study groups in NCT00604630
Study groupRoleWhat they receive
placeboPlacebo comparator50ml 0.9% NaCL
Receives: Drug: 0.9% NaCl
verumActive comparatorerythropoietin alfa 40,000 IU iv in 50ml 0.9% NaCl
Receives: Drug: recombinant human erythropoietin alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neurological/functional outcome as measured by the Barthel Index (BI)

    Measured: day 90

Secondary outcomes (17)
  1. Modified Rankin Scale (mRS) responder

    Measured: day 90

  2. Barthel Index (BI)

    Measured: day 30

  3. mRS

    Measured: day30, day 90

  4. NIH Stroke Scale

    Measured: day 1, 3, 7, 30, 90

  5. Proportion of subjects with minimal disability (mRS 0-1)

    Measured: day 30, day 90

  6. All-cause mortality

    Measured: day 90

  7. Mortality directly related to stroke

    Measured: day 90

  8. Proportion of subjects with BI >= 95

    Measured: day 30, day 90

  9. Proportion of subjects with BI=100

    Measured: day 30, day 90

  10. Proportion of subjects with neurological recovery

    Measured: day 3, 7, 30, 90

  11. Distribution of mRS scores

    Measured: day 30, day 90

  12. Distribution of BI scores

    Measured: day 30, day 90

  13. Distribution of NIH Stroke Scale scores

    Measured: day 30, day 90

  14. Serum level of glial damage markers S100B and GFAP

    Measured: day 1, 2, 3, 4, 7

  15. Lesion size (MRI DWI, flair)

    Measured: day 1, day 7

  16. Overall survival

    Measured: day 90

  17. Late recovery index (BI day 90 versus BI day 30)

    Measured: day 30 to day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2008 (estimated)
  2. Study startJan 2003
  3. Primary completionJun 2008
  4. Study completionJun 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
522 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00604630
Sponsor's protocol ID
BfArM-4019639/2002
Other IDs
"EPO Stroke Study", "Ehrenreich EPO Stroke Study", "Ehrenreich Study"
Acronym
ESS
Status last verified
Sep 2008
First submitted
17 Jan 2008
Last updated
22 Oct 2008
Results posted
No
Data monitoring committee
Yes

Publications

  • Siren AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, Keenan S, Gleiter C, Pasquali C, Capobianco A, Mennini T, Heumann R, Cerami A, Ehrenreich H, Ghezzi P. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4044-9. doi: 10.1073/pnas.051606598. Epub 2001 Mar 20.

    PubMed 11259643
  • Ehrenreich H, Hasselblatt M, Dembowski C, Cepek L, Lewczuk P, Stiefel M, Rustenbeck HH, Breiter N, Jacob S, Knerlich F, Bohn M, Poser W, Ruther E, Kochen M, Gefeller O, Gleiter C, Wessel TC, De Ryck M, Itri L, Prange H, Cerami A, Brines M, Siren AL. Erythropoietin therapy for acute stroke is both safe and beneficial. Mol Med. 2002 Aug;8(8):495-505.

    PubMed 12435860
  • Lewczuk P, Hasselblatt M, Kamrowski-Kruck H, Heyer A, Unzicker C, Siren AL, Ehrenreich H. Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin. Neuroreport. 2000 Nov 9;11(16):3485-8. doi: 10.1097/00001756-200011090-00017.

    PubMed 11095504
  • Siren AL, Knerlich F, Poser W, Gleiter CH, Bruck W, Ehrenreich H. Erythropoietin and erythropoietin receptor in human ischemic/hypoxic brain. Acta Neuropathol. 2001 Mar;101(3):271-6. doi: 10.1007/s004010000297.

    PubMed 11307627
  • Herrmann M, Ehrenreich H. Brain derived proteins as markers of acute stroke: their relation to pathophysiology, outcome prediction and neuroprotective drug monitoring. Restor Neurol Neurosci. 2003;21(3-4):177-90.

    PubMed 14530580
  • Ehrenreich H, Hasselblatt M, Knerlich F, von Ahsen N, Jacob S, Sperling S, Woldt H, Vehmeyer K, Nave KA, Siren AL. A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain. Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):862-7. doi: 10.1073/pnas.0406008102. Epub 2005 Jan 10.

    PubMed 15642952
  • Siren AL, Radyushkin K, Boretius S, Kammer D, Riechers CC, Natt O, Sargin D, Watanabe T, Sperling S, Michaelis T, Price J, Meyer B, Frahm J, Ehrenreich H. Global brain atrophy after unilateral parietal lesion and its prevention by erythropoietin. Brain. 2006 Feb;129(Pt 2):480-9. doi: 10.1093/brain/awh703. Epub 2005 Dec 9.

    PubMed 16339796
  • Ehrenreich H, Hinze-Selch D, Stawicki S, Aust C, Knolle-Veentjer S, Wilms S, Heinz G, Erdag S, Jahn H, Degner D, Ritzen M, Mohr A, Wagner M, Schneider U, Bohn M, Huber M, Czernik A, Pollmacher T, Maier W, Siren AL, Klosterkotter J, Falkai P, Ruther E, Aldenhoff JB, Krampe H. Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. Mol Psychiatry. 2007 Feb;12(2):206-20. doi: 10.1038/sj.mp.4001907. Epub 2006 Oct 10.

    PubMed 17033631
  • Ehrenreich H, Fischer B, Norra C, Schellenberger F, Stender N, Stiefel M, Siren AL, Paulus W, Nave KA, Gold R, Bartels C. Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Brain. 2007 Oct;130(Pt 10):2577-88. doi: 10.1093/brain/awm203. Epub 2007 Aug 29.

    PubMed 17728357
  • Woywodt A, Gerdes S, Ahl B, Erdbruegger U, Haubitz M, Weissenborn K. Circulating endothelial cells and stroke: influence of stroke subtypes and changes during the course of disease. J Stroke Cerebrovasc Dis. 2012 Aug;21(6):452-8. doi: 10.1016/j.jstrokecerebrovasdis.2010.11.003.

    PubMed 21852153
  • Ehrenreich H, Weissenborn K, Prange H, Schneider D, Weimar C, Wartenberg K, Schellinger PD, Bohn M, Becker H, Wegrzyn M, Jahnig P, Herrmann M, Knauth M, Bahr M, Heide W, Wagner A, Schwab S, Reichmann H, Schwendemann G, Dengler R, Kastrup A, Bartels C; EPO Stroke Trial Group. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke. 2009 Dec;40(12):e647-56. doi: 10.1161/STROKEAHA.109.564872. Epub 2009 Oct 15.

    PubMed 19834012

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing recombinant human erythropoietin alfa and 0.9% NaCl in people with Infarction, Middle Cerebral Artery and Middle Cerebral Artery Stroke, run by Max-Planck-Institute of Experimental Medicine at 9 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neurological/functional outcome as measured by the Barthel Index (BI) (time frame: day 90). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00604630, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2008.

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